The kinetics of XRT both as a single modality and in concurrent therapy are so important and so evident in the
now totally unfashionable radbio literature. I have no doubt that there remain opportunities to markedly improve the therapeutic ratio here.
It's been a space for progressive XRT clinical research for like 50 years. Some notable victories in SCLC, prechemo NSCLC and pre-chemo head and neck CA (work is now 30+ years old).
This analysis of mature data confirms that CHART is superior to conventional radiotherapy in achieving local tumour control and survival in locally advanced NSCLC. This demonstrates the importance of cellular repopulation as a cause of failure in the radiotherapy of NSCLC. The reduction in the...
pubmed.ncbi.nlm.nih.gov
I suspect that timing is pretty important when integrating IO into XRT based therapy.
Never mind that intrafraction kinetics almost certainly matter...we just ignore this. (FLASH as an exception...but kinetics even among standard external beam formats can be widely variable)…check this out.
It's just both difficult to do this research and without significant financial support. Most trials will be negative (as is true for all truly progressive work). There's no pharma out there paying for it. It is not sexy (exempting the name FLASH).
Picking an estimated iso-effective dose schedule and then comparing to SOC fractionation with a non-inferiority trial is easy.
Although some such trials have stopped accrual early due to excess toxicity and been forgotten about.